Deltacel

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。百时美施贵宝（Bristol Myers Squibb）嵌合抗原受体（CAR）T细胞疗法Breyanzi再获FDA加速批准，用于治疗套细胞淋巴瘤（MCL）。原启生物（Oricell Therapeutics）的CAR-T药物OriCAR-017在治疗复发/难治性多发性骨髓瘤的1期临床试验中表现亮眼，患者的总缓解率达100%。全球首款肿瘤浸润淋巴细胞（TIL）疗法再传捷报，与PD-1抑制剂联用一线治疗晚期黑色素瘤的完全缓解率（CR）达30%。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF———✦研发进展✦———◇ 百时美施贵宝宣布，美国FDA已批准其CAR-T细胞疗法Breyanzi（lisocabtagene maraleucel；liso-cel）的扩展适应症，用于既往接受过至少2线系统性疗法的复发性或难治性套细胞淋巴瘤成人患者，包括曾接受过布鲁顿酪氨酸激酶（BTK）抑制剂治疗的患者。根据新闻稿，Breyanzi是首个获美国FDA批准用于治疗四种不同亚型非霍奇金淋巴瘤的CAR-T疗法，使之能够治疗广泛的B细胞恶性肿瘤患者群体。在支持Breyanzi此次获批的临床试验中，根据2014 Lugano分类标准以及骨髓活检确认，85.3%（58/68）的患者有缓解，67.6%（46/68）的患者达到CR。51.4%的缓解者在12个月时仍保持缓解，38.8%的缓解者在18个月时仍保持缓解。Breyanzi是一种靶向CD19抗原的自体CAR-T细胞疗法，具有明确的组成和4-1BB共刺激域。它于2021年2月获FDA批准，用于治疗接受过两种或以上系统治疗的复发/难治性大B细胞淋巴瘤（LBCL）成人患者。Breyanzi在今年获加速批准用以治疗复发/难治性慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL）、复发/难治性滤泡性淋巴瘤（FL）成人患者。◇ Iovance Biotherapeutics公司公布了其TIL疗法Amtagvi（lifileucel）与PD-1抑制剂Keytruda（pembrolizumab）联合用于一线治疗晚期黑色素瘤的最新临床数据。分析显示，接受治疗的晚期黑色素瘤患者获得深度、持久的应答，患者的客观缓解率达65%，CR率达30%。Iovance已经启动3期临床试验TILVANCE-301，评估这一组合疗法一线治疗晚期黑色素瘤的效果。Lifileucel是基于患者自身的肿瘤浸润淋巴细胞构建的细胞疗法，其可识别并靶向多种患者特异性新抗原，以介导肿瘤细胞死亡。Lifileucel在今年2月获FDA加速批准用于治疗晚期黑色素瘤。该疗法是全球首款获批的TIL疗法，也是首款获批治疗实体瘤的T细胞疗法，是细胞疗法的又一里程碑。◇ Kiromic BioPharma公司公布了其在研γ-δ T细胞（GDT）疗法Deltacel（KB-GDT-01）用于治疗IV期转移性非小细胞肺癌（NSCLC）患者的1期临床试验的积极早期疗效数据。该研究中，第二个队列首名患者接受治疗六周后的初步结果显示，Deltacel在控制肿瘤生长方面具有有效性，并显示出良好的安全性和耐受性。扫描显示患者的疾病稳定，未发现新的转移灶，肿瘤缩小了8.5%。此外，Deltacel治疗使患者无需使用处方止痛药，生活质量得到改善。Deltacel是一种同种异体细胞治疗产品，由未经修饰的供体来源GDT组成。Deltacel旨在利用GDT的天然效力靶向实体瘤，最初的临床开发重点是NSCLC（约占肺癌病例的80%至85%）。两项临床前研究的数据表明，Deltacel与低剂量放射治疗相结合具有良好的安全性和有效性。◇ Be Biopharma公司宣布美国FDA批准了其潜在“first-in-class”的自体B细胞疗法（BCM）BE-101的IND申请。BE-101旨在将人类FIX基因插入原代人类B细胞，从而表达可治疗血友病B的活性FIX。在临床前研究中，单次使用BE-101已被证明能够提供具活性和持续的FIX水平。数据证实了表达FIX的BCM能够在骨髓组织中按预期分布，并能在骨髓组织中长期稳定地定植。此外，BE-101的可重复给药性也得到了证实，血浆FIX水平如预期增加。该公司计划在2024年下半年启动一项1/2期临床试验，以评估BE-101在中重度至重度血友病B成年患者中的安全性和初步疗效。◇ 原启生物公布了其靶向GPRC5D的CAR-T药物OriCAR-017治疗复发/难治性多发性骨髓瘤的1期临床试验的2年长期随访结果。截至2024年1月16日的数据，所有（10名）患者对OriCAR-017治疗应答良好，总缓解率为100.0%，严格完全缓解（sCR）率为80.0%，非常好的部分缓解率（VGPR）为20.0%。所有患者在第28天都达到了100%微小残留病灶阴性率（MRD），且在第3个月得到进一步检测确认为100%阴性。中位缓解持续时间（mDoR）为10.43个月；中位无进展生存期（mPFS）为11.37个月；中位总生存期（mOS）尚未达到。在高剂量组中（67%为BCMA CAR-T经治患者），其mDoR为17.23个月，mPFS为19.10个月。此外，OriCAR-017显示良好的安全性和耐受性。◇ 锐正基因公布了其体内基因编辑药物ART001治疗转甲状腺素蛋白淀粉样变性（ATTR）患者的24周临床安全性和药效观察结果。研究结果显示，给药后4周，高剂量组受试者外周TTR蛋白较基线即可平均下降90%以上；给药24周后，高剂量组受试者ART001药效稳定在90%以上，并初步显示出一次性给药即可获得长期持续药效的潜力。在安全性方面，10例受试者未发生输注相关反应，未发生与药物相关的严重不良事件或严重不良反应，也未见肝毒性和免疫毒性。在脱靶编辑方面，ART001在人体细胞实验中，即使超过饱和剂量近80倍，都检测不到脱靶编辑。ART001注射液为锐正基因自主研发，以脂质纳米颗粒（LNP）作为递送载体，将靶向TTR基因的基因编辑组件递送至肝脏，安全特异地编辑TTR基因，阻断TTR蛋白的表达，从而避免产生淀粉样物质异常沉积。———✦融资、合作、M&A✦———图片来源：123RF◇ Anocca公司与Shinobi Therapeutics公司宣布建立战略合作伙伴关系，将Shinobi公司专有的免疫逃避iPS-T细胞平台结合由Anocca公司发现并验证的新型候选T细胞受体（TCR），开发一类用于治疗实体瘤的新型现货型同种异体TCR工程iPS-T细胞疗法（TCR-iPS-T）。Shinobi公司的“Katana”技术能以即插即用的方式将抗原靶向TCR和/或CAR构建体有效地导入其免疫逃避iPS-T细胞。Anocca开发了一种独特的发现平台，利用可编程的人体细胞能够重建和操纵T细胞免疫，并提供高度特异性、可临床应用的TCR候选库，用于治疗实体瘤。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Be Biopharma Announces FDA Clearance of IND Application for BE-101 in Hemophilia B. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528592948/en[2] Kiromic BioPharma Reports Favorable Results at Six Weeks from Fourth Patient in Deltacel-01 Clinical Trial. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240529675813/en[3] U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. Retrieved May 30, 2024 from https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx[4] Iovance Biotherapeutics Announces Clinical Data in Frontline Advanced Melanoma at ASCO 2024 Annual Meeting. Retrieved May 24, 2024 from https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-data-frontline[5] 2024 ASCO: 原启生物OriCAR-017 口头报告摘要公布. Retrieved May 24 , 2024, from https://mp.weixin.qq.com/s/P7tofaL9SRqyv3zCJJcv6Q[6] 中国首个进入IIT临床研究的体内基因编辑产品锐正基因ART001将发布最新24周临床研究数据. Retrieved May 27 , 2024, from https://mp.weixin.qq.com/s/sD4xW6CJ8vamEK88IfckTQ[7] Anocca AB and Shinobi Therapeutics Announce Strategic Partnership to Develop Allogeneic TCR-T Cell Therapies in Oncology. Retrieved May 31, 2024 from https://www.globenewswire.com/news-release/2024/05/30/2890550/0/en/Anocca-AB-and-Shinobi-Therapeutics-Announce-Strategic-Partnership-to-Develop-Allogeneic-TCR-T-Cell-Therapies-in-Oncology.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Scans of this first patient in the second cohort show 8.5% reduction in tumor size HOUSTON--(BUSINESS WIRE)-- Kiromic BioPharma, Inc. (OTCQB: KRBP) (“Kiromic” or the “Company”) reports favorable safety and tolerability, and early efficacy in the fourth patient enrolled in the Company’s Deltacel-01 Phase 1 clinical trial. Deltacel-01 is evaluating Deltacel™ (KB-GDT-01), Kiromic’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies. Preliminary results of this first patient in the second cohort obtained six weeks after beginning treatment show a favorable safety and tolerability profile, while imaging shows promising early efficacy for the Deltacel™ treatment. Scans showed disease stabilization, no new sites of metastatic disease and an 8.5% reduction in the tumor size. Additionally, this patient experienced quality-of-life benefits from Deltacel treatment including stopping their previous need for prescription pain medication. This patient is being treated at the Beverly Hills Cancer Center (BHCC). “The fourth patient in Deltacel-01 suffered from metastatic squamous cell carcinoma. They were enrolled in this trial after failing chemotherapy, antibody-based immunotherapy and standard radiotherapy. The six-week follow-up visit revealed stable disease, no new lesions and an 8.5% reduction in tumor size compared with pre-treatment measurements. In addition, while at the time of study enrollment this patient was taking a medication for cancer pain, it was not necessary any longer after receiving Deltacel, indicating a quality-of-life improvement,” said Afshin Eli Gabayan, M.D., Medical Oncologist, Medical Director and Principal Investigator at BHCC. “These encouraging clinical findings represent a strong start to the second cohort in our Deltacel-01 trial. We are particularly encouraged by the reduction in size of the tumor observed in this patient, and by the significant improvement in quality of life as evidenced by the reduction in cancer-related pain. Our team remains committed to advancing Deltacel-01 and we look forward to reporting preliminary results from the remainder of the three-patient second cohort in June,” said Pietro Bersani, Chief Executive Officer of Kiromic BioPharma. About Deltacel-01 In Kiromic’s open-label Phase 1 clinical trial, titled “Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer” (NCT06069570), patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel™ with four courses of low-dose, localized radiation over a 10-day period. The primary objective of the Deltacel-01 trial is to evaluate safety, while secondary measurements include objective response, progression-free survival, overall survival, time to progression, time to treatment response and disease control rates. About Deltacel™ Deltacel™ (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of stage 4 metastatic NSCLC. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel™ is the leading candidate in Kiromic’s GDT platform. Deltacel™ is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial clinical focus on NSCLC, which represents about 80% to 85% of all lung cancer cases. Data from two preclinical studies demonstrated Deltacel™’s favorable safety and efficacy pro it was combined with low-dose radiation. About Beverly Hills Cancer Center As a private, academic, community-based cancer center, the Beverly Hills Cancer Center not only provides the latest state-of-the-art cancer treatments all under one roof, but also provides leading clinical trials and research, attracting patients globally. By providing access to groundbreaking clinical trials, the Beverly Hills Cancer Center offers patients the opportunity to participate in the most advanced cancer treatments currently in development in the world. Beverly Hills Cancer Center is comprised of an internationally recognized multidisciplinary medical team consisting of medical oncologists, radiation oncologists, radiologists, hematologists and internists who provide exceptional patient care and support services including a robust and highly efficient team of clinical research professionals. More information is available at . About Kiromic BioPharma Kiromic BioPharma, Inc. is a clinical-stage, fully integrated biotherapeutics company using its proprietary DIAMOND® artificial intelligence (AI) 2.0 target discovery engine to develop and commercialize cell therapies focusing on immuno-oncology. Kiromic is developing a multi-indication allogeneic cell therapy platform that exploits the natural potency of Gamma Delta T-cells to target solid tumors. Kiromic’s DIAMOND® AI is where data science meets target identification to dramatically compress the years and hundreds of millions of dollars required to develop a live drug. The Company maintains offices in Houston, Texas. To learn more, visit and connect with us on Twitter and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. Kiromic makes such forward-looking statements pursuant to the safe harbor provisions of the United States Private Securities Litigation Reform Act, Section 21E of the Securities Exchange Act of 1934, as amended, and other federal securities laws. All statements other than statements of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as: “will,” “potential,” “could,” “can,” “believe,” “intends,” “continue,” “plans,” “expects,” “anticipates,” “estimates,” “may,” or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements regarding: Kiromic’s ability to achieve its objectives and Kiromic’s financing strategy and availability of funds. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, the risks and uncertainties discussed in our Annual Report on Form 10-K for the year ended December 31, 2023, and as detailed from time to time in our other SEC filings. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance, or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. Such forward-looking statements relate only to events as of the date of this press release. We undertake no obligation to update any forward-looking statements except to the extent required by law.